Bireociclib Earns NMPA Approval in China For 2 Indications in HR+/HER2– Breast Cancer

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China’s National Medical Products Administration (NMPA) has approved bireociclib tablets (Xuanyuening) for 2 indications in hormone receptor–positive/HER2-negative breast cancer.1 The agent is the only CDK4/6 inhibitor approved in China as monotherapy for the later-line treatment of patients with hormone receptor–positive/HER2-negative advanced breast cancer.2

The agent is approved as monotherapy for adult patients with hormone receptor–positive/HER2-negative locally advanced or metastatic breast cancer who experienced disease progression following 2 or more prior lines of endocrine therapy and 1 chemotherapy regimen in the metastatic setting. The agent is also now indicated in combination with fulvestrant (Faslodex) for adult patients with hormone receptor–positive/HER2-negative advanced or metastatic breast cancer who experienced disease progression following previous endocrine therapy.

Bireociclib is multitargeted, acting on CDK2, CDK4, CDK6, and CDK9, which leads to blockage of the tumor cell proliferation pathway with reduced hematological toxicity.1

Data from the phase 2 BRIGHT-1 trial (NCT04539496) showed that patients with heavily pretreated hormone receptor–positive/HER2-negative advanced breast cancer who received bireociclib (n = 131) experienced an objective response rate (ORR) of 29.8% (95% CI, 22.1%-38.4%) per independent review committee assessment; all responses were partial.3 The median duration of response (DOR) was 15.2 months (95% CI, 9.5-not reached) and the median progression-free survival (PFS) was 11.0 months (95% CI, 7.3-12.9).

Findings from the final analysis of the phase 3 BRIGHT-2 (NCT05077449) presented during the 2025 AACR Annual Meeting demonstrated that patients with hormone receptor–positive/HER2-negative advanced breast cancer treated with bireociclib plus fulvestrant (n = 204) achieved an investigator-assessed median PFS of 14.69 months (95% CI, 11.07-20.21) compared with 7.33 months (95% CI, 5.49-11.04) among patients who received placebo plus fulvestrant (n = 101; HR, 0.542; 95% CI, 0.399-0.735; P < .0001).4 The median PFS per blinded independent central review committee (BICR) was 17.51 months (95% CI, 13.83-23.06) vs 7.29 months (95% CI, 5.49-9.46), respectively (HR, 0.462; 95% CI, 0.333-0.642; P < .0001).

BRIGHT-1 was an open-label study that enrolled patients with histologically confirmed locally advanced, recurrent, or metastatic HR-p/HER2− breast cancer that was not amenable to curative surgical resection across 29 centers in China.3 Eligible patients were also required to have at least 1 measurable lesion per RECIST 1.1 criteria, an ECOG performance status of 0 or 1, and adequate bone marrow and organ function. Following enrollment, all patients received oral bireociclib at a dose of 480 mg twice daily.

The primary end point was confirmed ORR per independent review committee. Secondary end points included PFS, DOR, overall survival (OS), disease control rate (DCR), and safety.

In terms of safety, all patients experienced any-grade treatment-emergent adverse effects (TEAEs) and 83.2% had grade 3 or higher TEAEs. The most common any-grade TEAEs included diarrhea (93.1%), decreased neutrophil count (87.0%), decreased white blood cell count (86.3%), and vomiting (78.6%).

BRIGHT-2 enrolled patients who were 18 to 75 years old with locally advanced, recurrent, or metastatic hormone receptor–positive/HER2-negative breast cancer who experienced disease progression on or after endocrine therapy.4 Patients also could not have received more than 1 chemotherapy regimen in the advanced setting, had to have an ECOG performance status of 0 or 1, and at least 1 measurable lesion per RECIST 1.1 criteria.

Eligible patients were randomly assigned 2:1 to receive 360 mg of oral bireociclib twice daily or placebo. Patients in both arms also received fulvestrant at a dose of 500 mg on days 1 and 15 of cycle1 and on day 1 of the subsequent cycles, in 28-day cycles.

The primary end point was investigator-assessed PFS. Secondary end points included PFS per BICR, OS, ORR, DCR, DOR, and safety.

Regarding safety, any grade and grade 3 or higher TEAEs occurred at rates of 100% and 62.3% in the combination arm. The most common any-grade TEAEs included diarrhea (92.6%), neutropenia (89.2%), and leukopenia (86.8%).

References

1. Xuanzhu Biopharm's Xuanyuening® (BireociclibTablets) approved for dual indications, bringing innovative breakthroughs to breast cancer treatment. News release. Sihuan Pharmaceutical. May 15, 2025. Accessed May 16, 2025. https://www.prnewswire.com/news-releases/xuanzhu-biopharms-xuanyuening-bireociclibtablets-approved-for-dual-indications-bringing-innovative-breakthroughs-to-breast-cancer-treatment-302457439.html
2. The class 1 innovative drug bireociclib tablets independently developed by Xuanzhu Biopharmaceutical, as monotherapy and in combination with fulvestrant, granted marketing authorization by NMPA for two indications in HR+/HER2- advanced breast cancer. News release. Sihuan Pharmaceutical. May 15, 2025. Accessed May 16, 2025. https://www1.hkexnews.hk/listedco/listconews/sehk/2025/0515/2025051501331.pdf
3. Wang J, Zhang Q, Sun T, et al. An open-label, single-arm, multicenter, phase II trial of bireociclib as monotherapy for heavily pretreated HR-positive, HER2-negative advanced breast cancer patients: BRIGHT-1 trial. Cancer Commun (Lond). Published online February 27, 2025. doi:10.1002/cac2.70009
4. Wang J, Zhang Q, Li H, et al. BRIGHT-2 final analysis: A phase III trial of bireociclib plus fulvestrant as second-line endocrine therapy for patients with advanced HR+/HER2-breast cancer. Cancer Res. 2025;85(suppl 2):CT099. doi:10.1158/1538-7445.AM2025-CT099